The embodiments described herein relate generally to medical devices and pharmaceutical compositions, and more particularly to drug products for delivery of dry powder medicaments.
Pressurized metered dose inhalation devices (pMDI) are well-known for delivering drugs to patients by way of their lungs. pMDI's are comprised of a pressurized propellant canister with a metering valve housed in a molded actuator body with integral mouthpiece. This type of inhalation device presents drug delivery challenges to patients, requiring significant force to actuate with inhalation and timing coordination to effectively receive the drug. pMDI's containing suspended drug formulations also have to be shaken properly by the patient prior to actuating to receive an effective dose of the drug. These relatively complicated devices also require priming due to low drug content in initial doses and can require cleaning by the patient. In some devices, an additional spacer apparatus is prescribed along with the pMDI to compensate for the timing coordination issue, thus creating additional complications related to the patient for, cleaning, storage and transport of the bulky spacer apparatus. While many patients are experienced operating pMDI's or pMDI's with spacers, new patients often experience a relatively significant learning curve to operate these devices properly.
Dry powder inhalation devices (DPI) are also well-known for delivering powderized drugs to the lungs. DPI technologies are either active involving external energy to break-up and aerosolize particles or, passive utilizing the patient's inspiratory energy to entrain and deliver the powder to the lungs. Some DPI technologies integrate electronics while others are fully mechanical. The powder drug storage formats are normally reservoir, individually pre-metered doses, or capsule based systems. Some known DPI devices include (or deliver) engineered drug particles, but in most known devices deliver a conventional blend of sized active pharmaceutical ingredient(s) (API) plus sized lactose monohydrate used as a bulking agent to aid in the powder filling process and as carrier particles to aid in delivery of the active pharmaceutical ingredient(s) to the patient. These API—lactose monohydrate blends among others require a means to break-up aggregates formed by attractive forces holding them together.
Some known devices for storing and delivering known dry powder formulations include a storage reservoir and a separate chamber within which the dry powder can be disaggregated in preparation for delivery to the patient. Such known systems, however, often include multiple pathways (e.g., from the reservoir to the preparation chamber), and thus can have diminished accuracy of the delivered dose due to undesired contact with pathway walls, inconsistency in withdrawing the dose from the reservoir, and the like.
Some known devices for storing and delivering known dry powder formulations rely, at least in part, on air flow produced by the patient inspiration (i.e., inhalation). Variation in the flow rates and velocities produced among the patient population, however, can cause variation in the delivered dose and/or fine particle fraction. Moreover, normal part-to-part variation, as well as variation caused during use (e.g., deformation or blocking of flow paths due to the patient gripping the device) can also lead to undesired variation in the airflow resistance and accuracy of the delivered dose, as well as the magnitude of fine particle fraction.
Additionally, some known dry powder delivery devices are susceptible to inconsistent performance resulting from variations in how different users interact with the device. Said another way, known dry powder delivery devices do not account for “human factors” in operation. For example, known dry powder delivery devices can be susceptible to variations in performance based on any one or all the following: tilting of the device (before or during use), failure to generate adequate flow and pressure drop (vacuum or negative pressure), failure by the user to actuate mechanisms completely and properly (and in the correct order), and failure to load drug cartridges, capsules or blisters properly. As one example, some known dry powder delivery devices include passageways that can be obstructed if a user inadvertently covers an inlet port or squeezes the body of the device with too much force.
Thus, a need exists for improved methods and devices for delivering dry powder drugs. Specifically, a need exists for a dry powder delivery device having improved accuracy, improved fine particle fraction, and ease of use and administration. A need also exists for improved methods of filling and assembling dry powder delivery devices.